Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2023; 29(1): 171-189
Published online Jan 7, 2023. doi: 10.3748/wjg.v29.i1.171
In vivo recognition of bioactive substances of Polygonum multiflorum for protecting mitochondria against metabolic dysfunction-associated fatty liver disease
Li-Ping Yu, Yan-Juan Li, Tao Wang, Yu-Xuan Tao, Mei Zhang, Wen Gu, Jie Yu, Xing-Xin Yang
Li-Ping Yu, Yan-Juan Li, Tao Wang, Yu-Xuan Tao, Mei Zhang, Wen Gu, Jie Yu, Xing-Xin Yang, College of Pharmaceutical Science, Yunnan University of Chinese Medicine, Kunming 650500, Yunnan Province, China
Li-Ping Yu, Yan-Juan Li, Tao Wang, Yu-Xuan Tao, Mei Zhang, Wen Gu, Jie Yu, Xing-Xin Yang, College of Pharmaceutical Science, Yunnan Key Laboratory of Southern Medicine Utilization, Kunming 650500, Yunnan Province, China
Author contributions: Yu LP, Li YJ, and Wang T contributed equally to this work; Li YJ wrote the manuscript; Li YJ, Yu LP, and Wang T performed the experiments; Tao YX and Zhang M provided technical support and suggestions; Yang XX, Yu LP, Zhang M, and Gu W participated in writing and modifying the manuscript; Yang XX and Yu J designed the study; and all authors approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 82060707 and 82104381; the Application and Basis Research Project of Yunnan China, No. 202201AW070016, 202001AZ070001-006, and 2019IB009; and the Young and Middle-aged Academic and Technological Leader of Yunnan, No. 202005AC160059.
Institutional animal care and use committee statement: Approval was obtained from the Ethical Committee on Animal Care and Experimentation of the Yunnan University of Chinese Medicine (R-06201965).
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
Data sharing statement: All data used to support the findings of this study are available from the corresponding author upon reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xing-Xin Yang, PharmD, Professor, College of Pharmaceutical Science, Yunnan University of Chinese Medicine, No. 1076 Yuhua Road, Kunming 650500, Yunnan Province, China. yxx78945@163.com
Received: September 7, 2022
Peer-review started: September 7, 2022
First decision: October 19, 2022
Revised: November 1, 2022
Accepted: December 5, 2022
Article in press: December 5, 2022
Published online: January 7, 2023
Processing time: 118 Days and 22.4 Hours
Abstract
BACKGROUND

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a severe threat to human health. Polygonum multiflorum (PM) has been proven to remedy mitochondria and relieve MAFLD, but the main pharmacodynamic ingredients for mitigating MAFLD remain unclear.

AIM

To research the active ingredients of PM adjusting mitochondria to relieve high-fat diet (HFD)-induced MAFLD in rats.

METHODS

Fat emulsion-induced L02 adipocyte model and HFD-induced MAFLD rat model were used to investigate the anti-MAFLD ability of PM and explore their action mechanisms. The adipocyte model was also applied to evaluate the activities of PM-derived constituents in liver mitochondria from HFD-fed rats (mitochondrial pharmacology). PM-derived constituents in liver mitochondria were confirmed by ultra-high-performance liquid chromatography/mass spectrometry (mitochondrial pharmacochemistry). The abilities of PM-derived monomer and monomer groups were evaluated by the adipocyte model and MAFLD mouse model, respectively.

RESULTS

PM repaired mitochondrial ultrastructure and prevented oxidative stress and energy production disorder of liver mitochondria to mitigate fat emulsion-induced cellular steatosis and HFD-induced MAFLD. PM-derived constituents that entered the liver mitochondria inhibited oxidative stress damage and improved energy production against cellular steatosis. Eight chemicals were found in the liver mitochondria of PM-administrated rats. The anti-steatosis ability of one monomer and the anti-MAFLD activity of the monomer group were validated.

CONCLUSION

PM restored mitochondrial structure and function and alleviated MAFLD, which may be associated with the remedy of oxidative stress and energy production. The identified eight chemicals may be the main bioactive ingredients in PM that adjusted mitochondria to prevent MAFLD. Thus, PM provides a new approach to prevent MAFLD-related mitochondrial dysfunction. Mitochondrial pharmacology and pharmacochemistry further showed efficient strategies for determining the bioactive ingredients of Chinese medicines that adjust mitochondria to prevent diseases.

Keywords: Fatty liver; Mitochondria; Pharmacodynamic ingredients; Polygonum multiflorum

Core Tip: We found that Polygonum multiflorum (PM) protected the mitochondrial ultrastructure and prevented oxidative stress and energy production disorder in the liver mitochondria to mitigate metabolic dysfunction-associated fatty liver disease (MAFLD). Eight chemicals were identified from the liver mitochondria of the PM-treated rats using a novel strategy based on mitochondrial pharmacology and pharmacochemistry. The constituents identified regulated mitochondria to alleviate MAFLD. Our results indicate that PM restored mitochondrial structure and function and alleviated MAFLD, which may be related to oxidative stress and energy production. The eight substances may be the main pharmacodynamic ingredients in PM that regulate mitochondria to prevent MAFLD.